Effective quadrupedal locomotion requires a close coordination between the spatially distant central pattern generators (CPGs) controlling forelimb and hindlimb movements. Using isolated preparations of the neonatal rat spinal cord, we explore the role of intervening thoracic circuitry in cervicolumbar CPG coordination and the contribution to this remote coupling of limb somatosensory inputs. In preparations activated with bath-applied N-methyl-D,L-aspartate, serotonin, and dopamine, the coordination between locomotor-related bursts recorded in cervical and lumbar ventral roots was substantially weakened, although not abolished, when the thoracic segments were selectively withheld from neurochemical stimulation or were exposed to a low Ca 2ϩ solution to block synaptic transmission. Moreover, cervicolumbar CPG coordination was reduced after a thoracic midsagittal section, suggesting that cross-cord projections participate in the anteroposterior coupling. In quiescent preparations, either cyclic or tonic electrical stimulation of low-threshold afferent pathways in C8 or L2 dorsal roots (DRs) could elicit coordinated ventral root bursting at both cervical and lumbar levels via an activation of the underlying CPG networks. When lumbar rhythmogenesis was prevented by local synaptic transmission blockade, L2 DR stimulation could still drive left-right alternating cervical bursting in preparations otherwise exposed to normal bathing medium. In contrast, when the cervical generators were selectively blocked, C8 DR stimulation was unable to activate the lumbar CPGs. Thus, in the newborn rat, anteroposterior limb coordination relies on active burst generation within midcord thoracic circuitry that additionally conveys ascending and weaker descending coupling influences of distant limb proprioceptive inputs to the cervical and lumbar generators, respectively.

During exercise and locomotion, breathing rate rapidly increases to meet the suddenly enhanced oxygen demand. The extent to which direct central interactions between the spinal networks controlling locomotion and the brainstem networks controlling breathing are involved in this rhythm modulation remains unknown. Here, we show that in isolated neonatal rat brainstem-spinal cord preparations, the increase in respiratory rate observed during fictive locomotion is associated with an increase in the excitability of pre-inspiratory neurons of the parafacial respiratory group (pFRG/Pre-I). In addition, this locomotion-induced respiratory rhythm modulation is prevented both by bilateral lesion of the pFRG region and by blockade of neurokinin 1 receptors in the brainstem. Thus, our results assign pFRG/Pre-I neurons a new role as elements of a previously undescribed pathway involved in the functional interaction between respiratory and locomotor networks, an interaction that also involves a substance P-dependent modulating mechanism requiring the activation of neurokinin 1 receptors. This neurogenic mechanism may take an active part in the increased respiratory rhythmicity produced at the onset and during episodes of locomotion in mammals.

Neural networks that can generate rhythmic motor output in the absence of sensory feedback, commonly called central pattern generators (CPGs), are involved in many vital functions such as locomotion or respiration. In certain circumstances, these neural networks must interact to produce coordinated motor behavior adapted to environmental constraints and to satisfy the basic needs of an organism. In this context, we recently reported the existence of an ascending excitatory influence from lumbar locomotor CPG circuitry to the medullary respiratory networks that is able to depolarize neurons of the parafacial respiratory group during fictive locomotion and to subsequently induce an increased respiratory rhythmicity (Le Gal et al., 2014b). Here, using an isolated in vitro brainstem-spinal cord preparation from neonatal rat in which the respiratory and the locomotor networks remain intact, we show that during fictive locomotion induced either pharmacologically or by sacrocaudal afferent stimulation, the activity of both thoracolumbar expiratory motoneurons and interneurons is rhythmically modulated with the locomotor activity. Completely absent in spinal inspiratory cells, this rhythmic pattern is highly correlated with the hindlimb ipsilateral flexor activities. Furthermore, silencing brainstem neural circuits by pharmacological manipulation revealed that this locomotor-related drive to expiratory motoneurons is solely dependent on propriospinal pathways. Together these data provide the first evidence in the newborn rat spinal cord for the existence of bimodal respiratory-locomotor motoneurons and interneurons onto which both central efferent expiratory and locomotor drives converge, presumably facilitating the coordination between the rhythmogenic networks responsible for two different motor functions.